GROWTH-INHIBITORY EFFECTS OF VITAMIN-D ANALOGS AND RETINOIDS ON HUMANPANCREATIC-CANCER CELLS

Retinoids and vitamin D are important factors that regulate cellular g rowth and differentiation. An additive growth-inhibitory effect of ret inoids and vitamin D analogues has been demonstrated for human myeloma , leukaemic and breast cancer cells. We set out to study the effects o f the vitamin D analogue EB1089 and the retinoids all-trans- and 9-cis -retinoic acid on the human pancreatic adenocarcinoma cell lines Capan 1 and Capan 2 and the undifferentiated pancreatic carcinoma cell line Hs766T. The cell lines investigated expressed vitamin D receptor, ret inoic acid receptor (RAR)-alpha and gamma as determined by polymerase chain reaction after reverse transcription. RAR-beta was expressed onl y in Hs766T cells. Addition of all-trans-retinoic acid increased the a mount of RAR-alpha mRNA in the three cell lines and induced RAR-beta m RNA in Capan 1 and Capan 2 cells. All-trans-retinoic acid at a concent ration of 10 nM inhibited the growth of Capan 1 and Capan 2 cells by 4 0% relative to controls. 9-cis-Retinoic acid was less effective. Neith er all-trans-retinoic acid nor 9-cis-retinoic acid affected the growth of Hs766T cells. EB1089, if added alone to the cells, did not signifi cantly inhibit growth. However, the combination of 1 nM EB1089 with 10 nM all-trans-retinoic acid exerted a growth-inhibitory effect of 90% in Capan 1 cells and of 70% in Capan 2 cells. Our data suggest that vi tamin D analogues together with retinoids inhibit the growth of human pancreatic cancer cells. However, in vivo studies are necessary to exa mine the potential use of retinoids and vitamin D analogues on pancrea tic cancer.